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Chronic L-DOPA administration is not toxic to the remaining dopaminergic
nigrostriatal neurons, but instead may promote their functional recovery,
in rats with partial 6-OHDA or FeCl(3) nigrostriatal lesions.

In this study, we have examined the effects of chronic
L-3,4-dihydroxyphenylalanine (L-DOPA) administration on the remaining
dopaminergic neurons in rats with 6-hydroxydopamine (6-OHDA) or buffered
FeCl(3) partial lesions to the nigrostriatal tract.

L-DOPA administration increased the turnover of dopamine in the striatum.

L-DOPA administration for 1 week produced an increase in the level of
striatal RTI-121 binding, a specific marker for dopamine uptake sites on
the dopaminergic nerve terminals in the striatum.

However, longer periods of L-DOPA treatment decreased the level of RTI-121
binding in the striatum.

In the partial 6-OHDA lesion model, L-DOPA treatment had a time-dependent
effect on the number of neurons demonstrating a dopaminergic phenotype
i.e., neurons that are tyrosine hyrdoxylase (TH)-immunopositive, on the
lesioned side of the brain.

In the first few weeks of treatment, L-DOPA decreased the number of
TH-positive neurons but with long-term treatment, i.e., 24 weeks, L-DOPA
increased the number of neurons demonstrating a dopaminergic phenotype.

Even in the buffered FeCl(3) infusion model, where the levels of iron were
increased, L-DOPA treatment did not have any detrimental effects on the
number of TH-positive neurons on the lesioned side of the brain.

Consequently, chronic L-DOPA treatment does not have any detrimental
effects to the remaining dopaminergic neurons in rats with partial lesions
to the nigrostriatal tract; indeed in the 6-OHDA lesion model, long-term
L-DOPA may increase the number of neurons, demonstrating a dopaminergic
phenotype.

Copyright 2001 Movement Disorder Society.

PMID: 11391735 [PubMed - in process]
Datla KP, Blunt SB, Dexter DT.
Parkinson's Disease Research Unit,
Department of Neuroinflammation,
Imperial College School of Medicine at Charing Cross Campus,
London, United Kingdom.
1: Mov Disord 2001 May;16(3):424-34
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list
_uids=11391735&dopt=Abstract


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